Archives of Gynecology and Obstetrics

, Volume 295, Issue 5, pp 1105–1118 | Cite as

Genetic polymorphism of MTHFR C677T with preterm birth and low birth weight susceptibility: a meta-analysis

  • Han Wu
  • Ping Zhu
  • Xingyi Geng
  • Zhong Liu
  • Liangliang Cui
  • Zhongchun Gao
  • Baofa JiangEmail author
  • Liping YangEmail author
Maternal-Fetal Medicine



This study aimed at clarifying the association of maternal and neonatal methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms with preterm birth (PTB) and low birth weight (LBW) susceptibility, respectively.

Materials and methods

A systematic search of Embase, Medline, China Biological Medicine Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang Database was performed before June, 2016. The frequencies of maternal and neonatal MTHFR C677T genotypes in the cases and controls and other information were extracted by two independent investigators. Odds ratios (ORs) with 95% confidence intervals (CIs) were adopted to estimate the relationships between MTHFR C677T polymorphisms and PTB as well as LBW by random or fixed effect models.


Twenty-five studies from 20 articles concerning maternal and neonatal MTHFR C677T gene polymorphism with PTB and LBW were included in this study. Maternal MTHFR C677T polymorphism was associated with PTB risk under allele contrast (T vs. C, OR = 1.36, 95% CI 1.02–1.81), homozygote (TT vs. CC, OR = 1.70, 95% CI 1.07–2.68), and recessive (TT vs. CT + CC, OR = 1.49, 95% CI 1.00–2.22) model, but not dominant or heterozygote model. Maternal MTHFR C677T polymorphism was also associated with LBW risk under allele contrast (OR = 1.69, 95% CI 1.25–2.28), homozygote (OR = 2.26, 95% CI 1.44–3.54), dominant (OR = 1.71, 95% CI 1.19–2.47), recessive (OR = 1.79, 95% CI 1.42–2.26) model, but not heterozygote model. No associations between neonatal MTHFR C677T polymorphism and PTB or LBW were found under all genetic models.


Identification of maternal MTHFR C677T mutation may play a key role for primary prevention of PTB as well as LBW and screening pregnant women of high risk in developing countries.


Methylenetetrahydrofolate reductase Preterm birth Low birth weight Polymorphism Meta-analysis 


Author contributions

H. Wu: Project development, Manuscript writing; P. Zhu: Results interpretation; X. Geng: Data collection; Z. Gao: Data collection; Z. Liu: Data analysis; L. Cui: Data analysis; B. Jiang: Project development, Manuscript revision; L. Yang: Project supervision, Manuscript revision.

Compliance with Ethical Standards


This study was funded by Shandong Provincial Natural Science Foundation, China (Grant Number ZR2015HM076).

Conflict of interest

Author H. Wu declares that he has no conflict of interest. Author P. Zhu declares that she has no conflict of interest. Author X. Geng declares that he has no conflict of interest. Author Z. Liu declares that he has no conflict of interest. Author L. Cui declares that she has no conflict of interest. Author Z. Gao declares that he has no conflict of interest. Author B. Jiang declares that he has no conflict of interest. Author L. Yang declares that she has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Han Wu
    • 1
  • Ping Zhu
    • 2
  • Xingyi Geng
    • 3
  • Zhong Liu
    • 3
  • Liangliang Cui
    • 3
  • Zhongchun Gao
    • 4
  • Baofa Jiang
    • 1
    Email author
  • Liping Yang
    • 1
    Email author
  1. 1.Department of Epidemiology, School of Public HealthShandong UniversityJinanChina
  2. 2.Jinan Maternity and Child Care HospitalJinanChina
  3. 3.Jinan Centers for Disease Control and PreventionJinanChina
  4. 4.Centre for Health Management and PolicyShandong UniversityJinanChina

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